Wolverton-Anti-TNFs, IL-12/23, IL-23s and IL-17s Flashcards
What are the two TNF receptors? Which has higher affinity for TNF-alpha?
P55 and P75
P55 5-fold higher affinity for TNF-alpha (but high dissociation rate)
What is the source of Etanercept? Adalimumab? Infliximab?
Etanercept: fully human
Adalimumab: fully human
Infliximab: Chimeric human-mouse
What is etanercept?
Etanercept is a dimeric fusion protein of p75 TNF receptor linked to Fc IgG 1
What does etanercept bind to
Binds to both TNF-α and TNF-β; binding to soluble and membrane bound TNF-α
What is adalimumab and its components
Fully human monoclonal antibody of IgG1
What does adalimumab bind to
TNF-α only
inhibits TNF binding to p55 and p75 transmembrane TNF receptor
What is infliximab and its components
Chimeric (25% mouse, 75% human) monoclonal antibody of IgG1 kappa
What does infliximab bind to?
TNF-α only, inhibits binding to soluble and transmembrane TNF receptor
What is certolizumab and its components
Recombinant human Fab’ antibody conjugated with polyethylene glycol
What does certolizumab bind to?
TNF-α only
binding to soluble and transmembrane bound TNF-α
What is the half life of etanercept
5 days
What is the standard dosing regimen for Etanercept for psoriasis?
50 mg twice weekly for 3 months then 50 mg weekly
What is the trade name for etanercept
Enbrel
What is the half life of infliximab?
7-days at 5mg/kg
What is the standard dosing regimen for inflixmab for psoriasis?
3–5 mg/kg per injection; typically given at baseline, 2 weeks, 6 weeks, then every 8 weeks thereafter
E.g. 210-350 for 70 kg person
What is the half life of adalimumab?
14 days
What is the dosing for adalimimab for psoriasis? for HS?
80 mg loading dose at baseline, 40 mg at 1 week, then 40 mg every 2 weeks thereafter
For HS-160, then 80 at week 2, then 40 at week 4 then 40 weekly after
What is the dosing for certolizumab
400 mg every 2 weeks;
200 mg every 2 weeks can be considered for patients <90 kg in weight (after initial loading dose)
What is the half life of certolizumab
14 days
List 5 conditions etanercept is FDA approved for? Name 2 TNF-treated conditions that it is NOT approved for
Etanercept:
1. RA
2. Psoriasis
3. PsA
4. JIA
5. Ank spond
NOT approved for IBD
RCT showed no efficacy for HS
List 4 dermatological conditions etanercept is used off-label to treat?
- Severe drug reactions-SJS/TEN
- Granulomatous dermatoses-sarcoid, generalized GA
- Vasculitis-PAN, GCA, takayasauas
- Neutrophilic dermatoses-behcets, PG
- PRP
What is the PASI75 efficacy for etanercept
50%
What ages is etanercept approved for?
2-17 and then adults
Name 8 contraindications for Anti-TNF therapy
- Active malignancy
- Active uncontrolled infection-e.g. active hep B>C, TB
- Hypersensitivity
- concurrent anakitnra medications
Relative
5. MS or another demyelinating d/o or strong fam hx
6. CHD-NYHA class III and above
7. Pregnant/breast feeding
What is the pregnancy category of Etanercept
B
Name 6 serious AE of TNF inhibitors to discuss with patients
- Increased risk lymphoma-debated, but probably there
- Increased risk NMSC
- Increased risk infections-e.g. fungal, TB reactivation in latent TB, Hep B reactivation in chronic carriers, sepsis
- Demyelinating d/o like MS, optic neuritis, or GBS (rare, case reports), no official link
- Worsening of CHF
- Autoimmunity-ANA/anti dsDNA induction, sometimes SLE
- Hematologic toxicity-rare
What is the paediatric dose of etanercept
0.8 mg/kg per week in divided doses
What is infliximab approved for
IBD
RA
Ank spond
JIA
PsO
PsA
What is the PASI75 efficacy for infliximab
80%
What is the rate of ADAs in etanercept, infliximab and adalimumab?
Etanercept- rare
Inflixmab 10% in RA patients, 38% in psoriasis
ADA-5%
Name 5 off label uses for infliximab
- HS
- Neutrophilic-PG, Behcets
- Vasculitis-systemic, refractory KD
- Granulomatous dermatoses
- PRP